There is increased interest in the synthesis of new degradable polymers that can be attributed, at least in part, to the growing use of synthetic polymers in medical applications. Degradable polymers are presently used in matrices for delivery of bioactive substances, as scaffolding in tissue engineering, in suture materials, for fracture fixation, in dental applications, as sealants, as well as in other applications. Ideally, these synthetic polymers should be capable of degradation and the degradation products should be compatible with the human body.
Drug delivery systems can also benefit from the use of degradable polymers, especially when they are designed so that they are incapable of releasing their agent or agents until they are placed in an appropriate biological environment. Depending upon the polymer, the environmental change can involve pH, temperature, or ionic strength, and the system can shrink, swell, or decompose upon a change in any of these environmental factors. Biodegradable polymers, for example, degrade within the body as a result of natural biological processes, eliminating the need to remove a drug delivery system after release of the active agent has been completed.
Most biodegradable polymers are designed to degrade as a result of hydrolysis of the polymer chains into biologically acceptable, and progressively smaller, compounds. In some cases, such as systems that employ polylactides, polyglycolides, or their copolymers, the polymers will eventually break down to lactic acid and glycolic acid, enter the Kreb's cycle, and be further broken down into carbon dioxide and water and excreted through normal processes. In some degradable polymer systems, the release rate can be tailored for the application. For example, in systems that use polyanhydrides or polyorthoesters, the degradation occurs primarily at the surface of the polymer, resulting in a release rate that is proportional to the surface area of the drug delivery system.
However, these biodegradable polymers do not allow for controlled degradation of the polymer. For example, the biodegradability of polyester polymers depends on the ability of the ester linkage in the polymer backbone to hydrolyze or decompose in the presence of water. Such polymers often do not allow for predictable control over the rate of degradation once the polymer is placed inside an aqueous environment. Moreover, such polymer systems do not typically permit one to vary the release rate following administration or implantation.
Thus, there is a need in the art for new compositions and methods of synthesizing polymers that are capable of degrading in a controlled manner, e.g., in response to changes in the local environment or external stimuli.